Fig. 8.

The IP3R1–GRP75–VDAC1 complex mediates ERS–mitochondria-associated ER membranes (MAM)–mitochondrial oxidative stress and plays an important role in diabetic atrial remodeling.

Pharmacological prevention of ERS from upstream by the chemical chaperone 4-PBA precludes mitochondrial oxidative stress and improves atrial remodeling in diabetes. Gene silencing or knockout of the key gene GRP75 of the MAMs inhibited ER–mitochondrial calcium transport, antagonizes mitochondrial oxidative stress and calcium overload, and improves diabetic atrial remodeling.